An approach to the A ring of neocarzinostatin chromophore via sequential carbometalation/anion capture
✍ Scribed by John M. Nuss; Barry H. Levine; Roger A. Rennels; Majid M. Heravi
- Publisher
- Elsevier Science
- Year
- 1991
- Tongue
- French
- Weight
- 264 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
An intramolecular palladium catalyzed carbometalation followed by anion capture achieves construction of a model comprising the A ring of the proposed structure of Neocarzinostatin Chromophore-A with sufficient functionality to elaborate the B ring and explore the likely mode of biological action.
The highly interesting structure1 and novel mode of biological action2 of the powerful antitumor antibiotic Neocarzinostatin Chromophore (NCS-Chr), 1, have made it an attractive target for both total synthesis and for the design of analogues which mimic its considerable biological activity.3 Important subgoals subsumed in this exotic target are the labile array of unsaturation, control of olefin geometry and position, formation of the strained bicyclo[7.3.0]dodecadienediyne nucleus and the installation of four stereogenic centers on the Cl2 core. We perceived that by exploiting the known selectivities of transitton metal mediated carbometalation, along with the entropic advantage of intramolecular formation of five membered rings, an acyclic precursor could be transformed in one operation to the NCS-Chr A ring with proper appendages for elaboration of the B ring.4 Our strategy 1s described m Scheme 1. This synthetic approach can easily access structurally modified analogues for the further elucidation of the biological action. The plan involves utilizing an intramolecular carbometalation to form the bond between Cl and C9; this is immediately followed by intermolecular capture of the resultant (Z)organometallic by an alkynyl tin to form the C7-C8 bond.536 Scheme 1. Structure of Neocatzlnostalln Chromophore and Plan for Assembly of the A Ring OH